Background/Purpose:  Differences in the pathogenesis of ACPA- versus ACPA+ rheumatoid arthritis are still poorly understood. In this study, we compared patterns of synovial changes in both disorders, and how they correlate with clinical parameters of disease activity.

Methods:  Semi-quantitative histological scores (0-3) on synovial hyperplasia, diffuse and perivascular lymphocytic infiltrates, vascular hypertrophy and fibrinoid necrosis were obtained retrospectively from 62 ACPA+ and 29 ACPA- synovial biopsies, obtained by needle-arthroscopy from the knee of rheumatoid arthritis patients. Clinical and biological indices of disease activity (DAS28-CRP, SDAI, CDAI and their individual components) were retrieved from the medical records at the time of biopsy (T0), and 6 months later. IL6 and IL6R immunostainings were performed on a subset of the samples. High-throughput transcriptomic data were available for 14 ACPA+ and 6 ACPA- patients.

Results: Synovial hyperplasia, vascular hypertrophy and fibrinoid necrosis scores were significantly higher in ACPA- compared to ACPA+ patients. Diffuse and perivascular lymphocytic infiltrates also scored higher in ACPA- patients, but the difference was not significant. Clinical and biological indices of disease activity were similar in both groups, as were IL6 and IL6R immunostaining quantifications. In ACPA+ patients, all (except vascular hypertrophy) histological scores correlated with clinical and/or biological scores of disease activity at T0. Fibrinoid necrosis in ACPA+ patients also correlated with disease activity 6 months later. By contrast, none of the histological scores displayed any correlation with disease activity measures in ACPA- patients. Transcriptomic analyses demonstrated a significant correlation between synovial hyperplasia and a T cell activation signature (e.g. IL6R, IL23R) in ACPA+ biopsies. This correlation was also present in ACPA- samples, but stronger correlations were found in this group with transcripts pointing at the activation of other T cell related pathways, such as IL10 and TGFβ2.

Conclusion:  Synovial biopsies from ACPA- versus ACPA+ rheumatoid arthritis patients display different histological characteristics and histoclinical correlations. In particular, synovial biopsies from ACPA- patients have a higher cellularity, yet are associated with similar clinical disease activity. Preliminary transcriptomic data point at the presence of regulatory cells in ACPA- synovial tissue, as a potential explanation to this discrepancy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/differences-in-histological-scores-and-histoclinical-correlations-in-acpa-versus-acpa-rheumatoid-arthritis-patients/